Index of drugs

Hypercholesterolemia.The drug is used as a supplement to dietary treatment, to lower elevated total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides in adults, adolescents and children 10 years or older with primary hypercholesterolaemia, including heterozygous familial hyperlipidemia or complex hyperlipidemia (mixed ) (corresponding to Fredrickson's type IIa and IIb hiperlipidemia) in the case of an inadequate response to diet and other non-pharmacological treatments. The drug is also used to lower total cholesterol and LDL-cholesterol in adults with a homozygous form of familial hypercholesterolaemia, as a therapy added to other lipid-lowering therapy (eg LDL cholesterol apheresis) or when it is unavailable.Prevention of cardiovascular diseases.Prevention of cardiovascular events in adults who are at high risk for the first such event. At the same time, action should be taken to reduce other risk factors.

1 tabl powl. contains 10 mg, 20 mg or 40 mg of Atorvastatin in the form of a Calcium salt.

A selective, competitive inhibitor of HMG-CoA reductase, an enzyme responsible for the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Atorvastatin reduces serum cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase activity, which in turn inhibits cholesterol biosynthesis in the liver and leads to an increase in LDL receptors on the hepatocytes cell membrane surface, thereby enhancing LDL uptake and catabolism. It reduces the production of LDL and the amount of LDL molecules, causes an intensified and sustained increase in LDL receptor activity and preferably changes the quality of circulating LDL molecules. Decreases LDL-cholesterol in patients with homozygous familial hypercholesterolaemia who have not usually responded to lipid-lowering therapy. Atorvastatin reduces total cholesterol (30-46%), LDL-cholesterol (41-61%), apolipoprotein B (34-50%) and triglycerides (14-33%) and increases HDL-cholesterol and apolipoprotein A1. It has been proven that lowering total cholesterol, LDL cholesterol and apolipoprotein B reduces the risk of cardiovascular events and cardiovascular mortality. After oral administration, atorvastatin is rapidly absorbed, reaching a maximum blood concentration after 1-2 h. The absolute bioavailability is about 12% and the systemic HMG-CoA reductase inhibitory activity is about 30%. Plasma proteins bind at least 98%. It is metabolized in the liver by cytochrome P-450 3A4 to ortho- and parahydroxylated derivatives and various beta-oxidation products. About 70% of the HMG-CoA reductase inhibitory activity in the blood is attributed to active metabolites. It is excreted in bile. T_0,5 is about 14 hours. T_0,5 HMG-CoA reductase inhibitory activity is 20-30 h, due to the effect of active metabolites. Renal failure does not affect the concentration of atorvastatin and its active metabolites in the blood, nor its effectiveness. The concentration of atorvastatin and its active metabolites in the blood is significantly increased (C_max approximately 16 times and AUC approximately 11 times) in patients with chronic alcohol-related liver injury (Child-Pugh B).

Hypersensitivity to the active substance or to any of the excipients. Active liver disease or unexplained, persistently elevated serum transaminase levels exceeding the 3-fold upper limit of normal (ULN). Pregnancy. Breastfeeding period. Women of childbearing potential not using effective methods of preventing pregnancy.

Before starting treatment, as well as periodically while using the drug, a check-up of liver function should be performed. Patients who develop signs and symptoms of liver damage should undergo liver function tests.Patients who have increased aminotransferase levels should be monitored until the disorder is resolved. In the case of persistent elevation of aminotransferases, greater than 3-fold GGN, a dose reduction or discontinuation of the drug is recommended. Caution should be exercised when administering atorvastatin to patients who consume significant amounts of alcohol and / or have history of liver disease. In patients without coronary disease with a recent stroke or TIA episode (transient ischemic attack), haemorrhagic strokes were more frequent in patients treated with atorvastatin 80 mg compared with placebo. The increased risk was particularly noted in patients who had a history of a previous hemorrhagic stroke or lacunar infarction at the time of the study - in these patients the risk and benefit ratio of atorvastatin 80 mg is unambiguous, therefore the potential risk of occurrence should be carefully considered before starting treatment. hemorrhagic stroke. Atorvastatin should be prescribed with caution to patients with predisposing factors for rhabdomyolysis; before initiating statin treatment, creatine kinase (CK) activity should be investigated in the following cases: renal dysfunction; Hypothyroidism; muscular diseases or the occurrence of hereditary muscular diseases in a family history; previous occurrence of muscle damaging effects following the use of statins or fibrates; liver disease and / or large amounts of alcohol; in the elderly (over 70 years) the need for such tests should be considered in the context of other risk factors for rhabdomyolysis; in situations in which plasma concentration may be increased, e.g. interactions and special patient groups, including genetic subgroups (in patients with a polymorphism of the OATP1B1-encoding gene, exposure to atorvastatin may be increased 2.4-fold). In such situations, the risk of starting treatment with respect to possible benefits should be considered, and clinical symptoms should be monitored. If the CK activity is significantly increased in the initial assay (> 5 times ULN), treatment should not be started. Patients should report muscle pain, cramps or muscle weakness during treatment, especially if accompanied by general malaise or fever. If these symptoms occur in a patient taking Atorvastatin, CK activity should be determined. If it is significantly increased (> 5 times ULN), the drug should be discontinued. If the muscle symptoms are significantly increased and cause patient discomfort on a daily basis, then discontinuation of treatment should be considered, even when the CK activity is <5 times ULN. If clinical symptoms resolve and CK activity returns to normal, re-inclusion of atorvastatin or another statin at the lowest dose and with close clinical monitoring may be considered. Treatment with atorvastatin must be discontinued if there is a significant increase in CK (> 10 times ULN) or when rhabdomyolysis occurs or is suspected. The risk of rhabdomyolysis increases with atorvastatin with medicines that may increase plasma concentrations of atorvastatin, such as strong CYP3A4 inhibitors or transport protein inhibitors (eg cyclosporine, telithromycin, Clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, Itraconazole, posaconazole and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc.). The risk of myopathy may also be increased when concomitant use of gemfibrozil and other derivatives of fibrin, Erythromycin, niacin and ezetimibe. If possible, consider replacing these drugs with an alternative (non-interacting) way of treatment. In cases where the combination of these medicines with atorvastatin is required, the benefits and risks of treatment should be carefully considered. If the patient is on medication increasing plasma atorvastatin levels, a lower starting dose of atorvastatin is recommended. For strong CYP3A4 inhibitors, a lower initial dose of atorvastatin should be considered and appropriate clinical observation is recommended. Co-administration of atorvastatin and fusidic acid is not recommended. If you suspect interstitial lung disease, statin therapy should be discontinued.Statin drugs increase blood Glucose levels and in some patients with a high risk of developing diabetes in the future, they may cause hyperglycemia of an intensity requiring appropriate diabetes care. This risk is however outweighed by the benefit of reducing the risk of developing vascular disease, so statin therapy should not be discontinued. Patients at risk (patients with fasting glucose 5,6-6,9 mmol / l, BMI> 30 kg / m²with increased triglycerides, hypertension) should be subjected to clinical and biochemical monitoring in accordance with national guidelines. There are no studies on the effects of the medicine on the development of children. Atorvastatin should not be used in children under 10 years of age.

Administration of the preparation during pregnancy and breast-feeding is contraindicated. Women of childbearing age should use effective methods of contraception.

Common: rhinitis, allergic reactions, hyperglycemia, headache, sore throat and larynx, nosebleeds, constipation, flatulence, dyspepsia, nausea, diarrhea, muscle pain, joint pain, pain in the limbs, muscle cramps, swelling of the joints , back pain, abnormal liver function tests, increase in creatine kinase in the blood. Uncommon: hypoglycaemia, weight gain, anorexia, nightmares, insomnia, dizziness, paresthesia, hypoesthesia, dysgeusia, amnesia, blurred vision, tinnitus, vomiting, pain in the upper and lower abdomen, belching in the return of gastric contents , pancreatitis, hepatitis, urticaria, rash, pruritus, alopecia, neck pain, muscular fatigue, malaise, weakness, chest pain, peripheral edema, fatigue, fever, presence of white blood cells in the urine. Rare: thrombocytopenia, peripheral neuropathy, visual disturbances, cholestasis, angioneurotic edema, bladder rash (including erythema multiforme), Stevens-Johnson syndrome and toxic epidermal necrolysis, myopathy, myositis, rhabdomyolysis, tendon disorders occasionally complicated by tendon rupture. Very rare: anaphylaxis, hearing loss, liver failure, gynecomastia. During the use of atorvastatin, an increase in serum transaminases was observed (these changes were usually mild and transient and did not require discontinuation of therapy). Clinically important (> 3 times ULN), serum transaminases increased in 0.8% of patients (dose-dependent and reversible in all patients). Increased serum CK (> 3 times ULN) was reported in 2.5% of patients. Increased CK (> 10 times ULN) occurred in 0.4% of patients. Side effects characteristic of statins: sexual dysfunction, depression, individual cases of interstitial lung disease (especially during long-term treatment), diabetes (frequency depends on the presence or absence of risk factors: fasting glucose level ≥5,6 mmol / l, BMI> 30 kg / m², increased triglyceride levels, a history of hypertension).Children. Common: headache, abdominal pain, increased ALT, increased creatine phosphokinase in the blood. Based on the available data, it can be expected that the frequency, type and severity of side effects in children will be the same as in adult patients. Data on long-term safety in children are limited.

Orally. Doses should be adjusted individually depending on the concentration of LDL-cholesterol before starting treatment and the intended therapeutic goal and patient's response to treatment. The usual starting dose is 10 mg once a day. Dose modifications should be made every 4 weeks or less frequently. The maximum dose is 80 mg once a day.Primary hypercholesterolemia and mixed hyperlipidemia: the majority of patients will receive a dose of 10 mg once a day. The therapeutic response is observed within 2 weeks, and the maximum response is usually achieved within 4 weeks. It is maintained during long-term treatment.Heterozygous familial hypercholesterolaemiaThe recommended starting dose is 10 mg daily. Doses should be determined individually, and changes should be made every 4 weeks, up to a dose of 40 mg per day. You can either increase the dose to a maximum of 80 mg daily or administer 40 mg of atorvastatin daily in combination with bile acid sequestrants.Homozygous familial hypercholesterolaemia10-80 mg daily. Atorvastatin should be used in these patients as adjunctive therapy to other lipid-lowering therapy (eg LDL apheresis), or when such treatments are not available.Prevention of cardiovascular diseases: 10 mg daily. To obtain LDL-C, higher doses may be required for current guidelines. In patients with impaired renal function, no dose adjustment is necessary.Children and youth. Hypercholesterolemia: the use of the drug should be under the control of specialist doctors experienced in the treatment of hyperlipidemia in children. Regularly assess the health of patients in terms of treatment effectiveness. In the population of patients aged 10 years or older, the recommended starting dose is 10 mg per day. The dose may be increased to 20 mg a day depending on the response to treatment and tolerability. Safety data for children receiving doses higher than 20 mg, equivalent to approximately 0.5 mg / kg are limited. Data on the use of the drug in children aged 6-10 are limited; atorvastatin should not be used in children under 10 years of age. The preparation can be taken at any time of the day, regardless of meals; Table. you can chew or swallow whole.